Transcriptional Down-regulation of Tumor Necrosis Factor-α Gene by Early Given Pentoxifylline: A Quantitative Demonstration in Rats with Peritoneal Sepsis

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Effects of pentoxifylline (PTX; 20 mg/kg/day) on mortality, blood pressure, acidosis, and inflammatory mediators were studied in rats subjected to cecal ligation and puncture (CLP). PTX was in travenously given once 30 min after CLP. Compared with controls with CLP but no drug, the PTX group showed improved survival ever 10 days of observation. PTX treatment significantly attenuated the decrease in blood pressure and increase in serum lactate concentrations in comparison to controls administrated with normal saline at 24 h after operation. Tumor necrosis factor (TNF)-α concentrations were reduced significantly by PTX in serum measured by radioimmunoassays. According to the semi-quantitative and quantitative (TaqMan) reverse-transcription polymerase chain reactions, PTX had significantly decreased TNF-α but not IL-1β gene expression in lung and liver (both p＜0.05) at 24 h postoperatively. Thus, PTX attenuated mortality, TNF-α, and lactate in this sepsis model, in association with down-regulation of TNF gene transcription. Moreover, PTX may have other various benefitical actions on sepsis. Clinical trials of PTX given early in sepsis should be considered.